Синтез З'-дезоксипроизводных (2'-5')-олигоаденилатов, содержащих модифицированные гетерооснования

New derivatives of natural (2'-5')-oligoadenylates included double modifications in oligomer molecule have been synthesized. The synthesized compounds contain the ribavirin fragment or BAP-riboside as 5'-terminal or central nucleoside unit and 3'-deoxyadenosine (cordicepine) fragment at the 2'-end of oligomer chain. The modified (2'-5')-oligoadenylates have been obtained by the triester method. The compounds prepared may be of interest for investigation as antiviral agents in agriculture and medicine.Получены новые производные природных (2'-5')-олигоаденилатов, содержащие двойные модификации в молекуле олигомера, а именно включающие фрагмент рибавирина либо БАП-рибозида в качестве центрального либо 5'-концевого нуклеозидного звена, а также остаток 3'-дезоксиаденозина (кордицепина) в 2'-терми-нальном звене цепи. Синтез модифицированных (2'-5')-олигонуклеотидов осуществлен триэфирным методом. Полученные соединения представляют интерес для изучения в качестве противовирусных агентов в растениеводстве и медицине

ФАРМАКОКИНЕТИЧЕСКИЕ СВОЙСТВА И ЭНЗИМАТИЧЕСКИЙ ГИДРОЛИЗ ДИАЦИЛГЛИЦЕРОФОСФАТНЫХ ПРОИЗВОДНЫХ ФЛУДАРАБИНА

It is shown that the intragastric administration of 1,2- and 1,3-diacylglycerphosphate fludarabine derivatives to Wistar rats and ICR outbred mice leads to a prolonged circulation of fludarabine in animal serum in comparison with the analogous administration of equimolar fludarabine phosphate. The investigated compounds can be regarded as oral fludarabine prodrugs. It is found that the oral bioavalability of fludarabine from its 1,2-dimyristoylglycerophosphate derivative is close to its oral bioavalability from equimolar fludarabine phosphate. Based on the data of the model in vitro experiments, we can suppose that fludarabine can release from its diacylglycerphosphate prodrugs under the action of phospholipases A and D and phosphodiesterases.Установлено, что в результате внутрижелудочного введения 1,2- и 1,3-диацилглицерофосфатных производных флударабина крысам Вистар и аутбредным мышам наблюдается пролонгированное выделение и более длительная циркуляция нуклеозида в системном кровотоке животных, чем после введения эквимолярных количеств флударабина фосфата. Изученные фосфолипидные производные могут рассматриваться в качестве пероральных пролекарств флударабина. Показано, что оральная биодоступность флударабина из его 1,2-димиристоилглицерофосфатного производного у животных близка к его оральной биодоступности из эквимолярного количества флударабина фосфата. На основании данных, полученных в модельных экспериментах in vitro, можно предположить, что флударабин может выделяться из полученных пролекарств под действием ферментов, принадлежащих к семействам фосфолипаз А и Д, а также фосфодиэстераз

Коморбидность ахалазии пищевода, смешанной тревожной и депрессивной реакции у пациентки молодого возраста: проблемы диагностики и лечения

Achalasia cardia (“cardiospasm”, “phrenospasm”, “dolichoesophagus”, “megaesophagus”, “stenosis of cardia”) represents a primary impairment of esophageal motor function associated with impaired lower esophageal sphincter relaxation and peristalsis defects of the thoracic esophagus. It is diagnosed at the age of 25 to 60 years, making up to 20% of all diseases of the esophagus, and is characterized by a triad of symptoms: dysphagia, regurgitation and chest pain when swallowing. In most cases the first manifestations of achalasia are preceded by stress situations in the anamnesis that complicates the differential diagnosis of psychogenic esophageal spasm. The presented clinical case illustrates difficulties of early diagnosis of achalasia cardia in a young femalepatient with severe anxiety and depressive symptoms which develop under conditions of chronic stressful situations in the family or at work. The issues of interdisciplinary interaction of health professionals (physician, gastroenterologist, psychiatrist, psychotherapist, and surgeon) on the course of examination and management of patients with comorbid physical and mental pathology are discussed. The efficiency of the integrative approach to treatment and rehabilitation with the use of modern reconstructive surgical interventions as well as conservative methods of therapy, psychopharmacotherapy and personality-oriented psychotherapy proves the relevance of studying psychosomatic aspects of achalasia cardia.Ахалазия кардии (кардиоспазм, френоспазм, долихоэзофагус, мегаэзофагус, кардиостеноз) представляет собой первичное нарушение двигательной функции пищевода, связанное с ухудшением расслабления нижнего пищеводного сфинктера и дефектами перистальтики его грудного отдела. Диагностируется в возрасте 25–60 лет, составляя до 20% случаев всех заболеваний пищевода, характеризуется триадой симптомов: дисфагией, регургитацией, загрудинными болями при глотании. В большинстве случаев первым проявлениям ахалазии предшествуют стрессовые ситуации в анамнезе, что затрудняет дифференциальную диагностику с психогенным эзофагоспазмом. Представленный клинический случай иллюстрирует трудности диагностики ахалазии кардиального отдела пищевода у женщины молодого возраста с выраженной тревожной и депрессивной симптоматикой, развившейся в условиях хронической стрессовой ситуации семейного и производственного плана. Обсуждаются вопросы междисциплинарного взаимодействия специалистов (терапевта, гастроэнтеролога, психиатра, психотерапевта, хирурга) по тактике обследования и ведения больной с коморбидной соматической и психической патологией. Эффективность интегративного подхода к лечению и реабилитации с использованием современных реконструктивных хирургических вмешательств, а также консервативных методов терапии, психофармакотерапии, личностно ориентированной психотерапии свидетельствует об актуальности изучения психосоматических аспектов ахалазии кардии

Cerebral metastases of endometrial carcinoma. Diagnostic and neurosurgical aspects

Central nervous system (CNS) involvement by endometrial carcinoma is uncommon. Among 1710 patients registered for brain metastases at our institution between 1990 and 2012, 3 (0.18 %) developed brain metastases. All lesions (1 multiple, 2 single) were contrast enhancing on com- puted tomography scans, and were located in the cerebrum (lobus occipitalis) in 2 cases. The CNS was the only site of detectable disease in 1 patient with recurrent disease. One patient received radiotherapy (survival, 3 months) and two underwent surgical resection of solitary metas- tasis followed by radiotherapy (survival = 3 and 5 months and alive to the present). Prognosis of patients with CNS metastases from endometrial carcinoma appears poor; however, in a selected group of patients early diagnosis followed by multimodal treatment may result in a palliation of the disease

Neutron activation determination of gold in technogenic raw materials with different mineral composition

The methods used to determine the gold content in the technogenic objects of gold mining were analyzed regarding their non-homogeneity and complexity of chemical and mineral compositions. A possible application of the neutron activation analysis with the use of the californium source of neutrons for determining the content of fine-grained and extra-fine-grained gold in the technogenic objects, including the bottom-ash waste of energy providers, is considered. It was demonstrated that the chemical composition of the sample affects the neuron flux distribution in the sample, which can essentially distort the results of the neutron activation analysis. In order to eliminate possible systematic errors investigations of the effect of the sample mineral composition on the results of the gold determination using the neutron activation analysis were carried out. Namely, a large mass of rock (3-5 kg) was loaded into an activation zone using four matrix types such as silicate, carbon-containing, iron-containing, and titanium magnetite. It was shown that there wereno significant difference between the dispersal of the fluxes of thermal and resonance neutrons emitted from 252Cf during activation of the gold-containing technogenic samples with different mineral compositions

BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

Hepatocellular carcinoma ranks 5th in prevalence and 3rd in cancer mortality worldwide. The prognosis of this disease is very poor: the 5-year survival rate was not more than 3–5%. Metastases generally occur in the lung, in the lymph nodes of the abdomen, chest, and neck, in the vertebrae, kidneys, and adrenals. The cases of brain metastasis from hepatocellular cancer are very rare. Overall, the prognosis is very poor for patients with brain metastases from hepatocellular carcinoma. Nevertheless, solitary brain metastases and good hepatic function are favorable survival criteria; thus, the treatment of this group of patients may lead to their better survival. The paper describes a clinical case of brain metastasis from hepatocellular carcinoma in a patient receiving the combination treatment involving neurosurgical treatment and targeted therapy

POSSIBILITIES FOR RADIODIAGNOSIS OF TUBERCULOUS SPONDYLITIS

The presented case illustrates the possibilities of complex radiodiagnosis in a patient with tuberculous spondylitis. The specific features of displaying a spinal tuberculous lesion during X-ray study, tomosynthesis, computed tomography, and magnetic resonance imaging are described. A rational algorithm for the examination and treatment of patients with this disease is proposed, by comparing the clinical manifestations of spinal tuberculous lesion and the results of its radiological studies

New roentgen technologies (tomosynthesis) for diagnostics and outcomes evaluation of genital tuberculosis treatment

This article describes the specific primary disorder of small pelvis organs in the female patient with no tuberculosis in her medical history. Use of this roentgen technique for genital tuberculosis detection and assessment of treatment efficacy enhances the effectiveness of diagnostic activities and allows early detection of this pathology thus reducing the risk of complications which is crucial for pregnancy planning given the young age of the patient

CEREBRAL METASTASES CANCER OF THE LARYNX: TWO CASE REPORTS

Cerebral metastases cancer of the larynx are rare and poorly understood pathology, many questions of diagnostics and treatment of this pathology remain open. In the work presents clinical cases сerebral metastases cancer of the larynx. Special attention is paid to surgical treatment in complex with chemotherapy